Journal of Oral Pathology & Medicine最新文献_第3页

Circ_0004771 regulates malignant biological behaviors and has clinical significance in oral squamous cell carcinoma Circ_0004771 在口腔鳞状细胞癌中调控恶性生物学行为并具有临床意义。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-06-17 DOI: 10.1111/jop.13566

Rongji Shi, Lei Zhang

Background

The incidence of oral squamous cell carcinoma (OSCC) is increasing, and more effective treatment protocols must rapidly be developed to prevent the death of patients and ensure favorable outcomes. CircRNAs are a unique class of noncoding ribonucleic acid (RNA) molecules unaffected by RNA exonucleases. CircRNAs have more stable expression than linear RNAs and are not readily degraded; therefore, they are the newest focus of RNA research. Here, we analyze the mechanism of hsa_circ_0004771 (circ_0004771) in OSCC to provide a clinical reference.

Methods

Circ_0004771 expression was measured in peripheral blood, cancerous tissues and adjacent tissues of OSCC patients. Patients were followed up for 3 years. The diagnostic value of circ_0004771 for OSCC occurrence, prognosis, recurrence and survival was analyzed with receiver operating characteristic (ROC) curves. OSCC cells were lentivirally transduced with a circ_0004771-silencing or an empty vector to evaluate alterations in cell growth, invasion, and apoptosis. Apoptosis-related and epithelial–mesenchymal transition (EMT)-related protein expression was quantified. BALB/c nude mice were used for tumorigenesis experiments to evaluate tumor growth in vivo after silencing circ_0004771.

Results

Circ_0004771 expression was higher in peripheral blood and cancerous tissue of OSCC patients than in control peripheral blood and paracancerous tissue, respectively, exhibiting excellent predictive value for OSCC occurrence, prognosis, recurrence and survival. Silencing circ_0004771 decreased the growth, invasiveness, and EMT capacity and increased the apoptosis of OCC cells. In mice implanted with OSCC cells transduced with the circ_0004771-silencing lentiviral vector, the tumor growth capacity was obviously decreased.

Conclusion

Silencing circ_0004771 inhibits the malignant growth of OSCC.

背景：口腔鳞状细胞癌（OSCC）的发病率正在上升，必须迅速开发出更有效的治疗方案，以防止患者死亡并确保良好的预后。CircRNA 是一类独特的非编码核糖核酸（RNA）分子，不受 RNA 外切酶的影响。与线性 RNA 相比，CircRNA 的表达更稳定，而且不易降解，因此是 RNA 研究的最新热点。在此，我们分析了hsa_circ_0004771（circ_0004771）在OSCC中的作用机制，为临床提供参考：方法：检测 OSCC 患者外周血、癌组织和邻近组织中 Circ_0004771 的表达。对患者进行了为期 3 年的随访。用接收者操作特征曲线（ROC）分析了circ_0004771对OSCC发生、预后、复发和生存的诊断价值。用circ_0004771沉默载体或空载体慢病毒转导OSCC细胞，以评估细胞生长、侵袭和凋亡的变化。对细胞凋亡相关蛋白和上皮-间质转化（EMT）相关蛋白的表达进行了量化。用 BALB/c 裸鼠进行肿瘤发生实验，评估沉默 circ_0004771 后体内肿瘤的生长情况：结果：Circ_0004771在OSCC患者外周血和癌组织中的表达分别高于对照组外周血和癌旁组织，对OSCC的发生、预后、复发和生存具有很好的预测价值。沉默circ_0004771可降低OCC细胞的生长、侵袭性和EMT能力，增加其凋亡。小鼠植入转导了circ_0004771沉默慢病毒载体的OSCC细胞后，肿瘤生长能力明显下降：沉默circ_0004771可抑制OSCC的恶性生长。

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引用次数: 0

CD4+CD8αα+ is the dominant phenotype of intraepithelial lymphocytes and regulated by ThPOK and Runx3 in oral lichen planus CD4+CD8αα+ 是口腔扁平苔藓上皮内淋巴细胞的主要表型，并受 ThPOK 和 Runx3 的调控。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-06-12 DOI: 10.1111/jop.13564

Chao-Fan Bao, Fang Wang, Dong-Yang Zhou, Gang Zhou

Background

Oral lichen planus (OLP) is a common T cell-mediated oral mucosal immune inflammatory disease. Intraepithelial lymphocytes (IELs) are a unique subset of T cells that play an important role in regulating immune response. This study aims to investigate the phenotype and the differentiation mechanism of IELs in OLP.

Methods

The expression of CD4, CD8α, CD8β, T-helper-inducing POZ/Krueppel-like factor (ThPOK), and RUNX family transcription factor 3 (Runx3) in the epithelium and peripheral blood mononuclear cells (PBMCs) of OLP was determined by immunofluorescence and immunohistochemistry. Then, the correlations among them were analyzed. Naïve CD4⁺ T cells were sorted from blood of OLP patients and stimulated with retinoic acid (RA) and transforming growth factor-β₁ (TGF-β₁). Then the expression of CD4, CD8α, CD8β, ThPOK, and Runx3 was investigated by immunocytochemistry.

Results

CD8α expression and CD8αα⁺ cells were upregulated in the epithelium of OLP, whereas they were downregulated in PBMCs of OLP. CD8β was not expressed in the epithelium of OLP. CD4, CD8α, and Runx3 expression and CD4⁺CD8α⁺ cells were increased, whereas ThPOK expression was decreased in the epithelium of OLP. CD8α expression was positively correlated with Runx3 expression, whereas ThPOK expression was negatively correlated with Runx3 expression. After RA and TGF-β₁ stimulation, CD8α and Runx3 expression was upregulated, and ThPOK expression was downregulated in naïve CD4⁺ T cells.

Conclusion

CD4⁺CD8αα⁺ IELs may be the dominant phenotype of IELs in OLP, and the differentiation of CD4⁺CD8αα⁺ IELs in OLP is negatively regulated by ThPOK and positively regulated by Runx3.

背景：口腔扁平苔藓（OLP）是一种常见的由T细胞介导的口腔黏膜免疫炎症性疾病。上皮内淋巴细胞（IELs）是一种独特的T细胞亚群，在调节免疫反应中发挥着重要作用。本研究旨在探讨上皮内淋巴细胞在OLP中的表型和分化机制：方法：采用免疫荧光和免疫组织化学方法检测OLP上皮细胞和外周血单核细胞（PBMCs）中CD4、CD8α、CD8β、T-helper-inducing POZ/Krueppel-like因子（ThPOK）和RUNX家族转录因子3（Runx3）的表达。然后分析了它们之间的相关性。从 OLP 患者的血液中分拣出幼稚 CD4+ T 细胞，并用维甲酸（RA）和转化生长因子-β1（TGF-β1）进行刺激。然后用免疫细胞化学法检测 CD4、CD8α、CD8β、ThPOK 和 Runx3 的表达：结果：CD8α表达和CD8αα+细胞在OLP上皮细胞中上调，而在OLP的PBMCs中下调。CD8β 在 OLP 上皮细胞中没有表达。OLP上皮细胞中CD4、CD8α和Runx3的表达以及CD4+CD8α+细胞增加，而ThPOK的表达减少。CD8α 表达与 Runx3 表达呈正相关，而 ThPOK 表达与 Runx3 表达呈负相关。RA和TGF-β1刺激后，CD8α和Runx3的表达上调，而CD4+T细胞的ThPOK表达下调：结论：CD4+CD8αα+ IELs可能是OLP中IELs的主要表型，而OLP中CD4+CD8αα+ IELs的分化受ThPOK的负调控和Runx3的正调控。

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引用次数: 0

MiR-26a and miR-191 are upregulated while PLAG1 and HIF2 are downregulated in pleomorphic adenomas of the salivary glands compared to Warthin tumors 与 Warthin 肿瘤相比，唾液腺多形性腺瘤中 MiR-26a 和 miR-191 上调，而 PLAG1 和 HIF2 下调。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-06-09 DOI: 10.1111/jop.13565

Jelena Carkic, Nadja Nikolic, Violeta Sango, Nicole Riberti, Boban Anicic, Jelena Milasin

Background

Salivary gland tumors (SGTs) are a heterogenous group of pathologies, which still represents a challenge regarding differential diagnosis and therapy. Although histological findings govern SGTs management, detection of molecular alterations is emerging as an effective additional tool. The aim of this study was to analyze the relative expression levels of three micro RNAs (miR-26a, miR-26b, and miR-191), and three pro-oncogenic molecular markers (PLAG1, MTDH, and HIF2) in SGTs and normal salivary gland (NSG) tissues and evaluate them as potential differential diagnosis markers.

Methods

This cross-sectional study included 58 patients with SGTs (23 pleomorphic adenomas, 27 Warthin tumors, and 8 malignant SGTs) and 10 controls (normal salivary gland tissues). Relative gene expression levels of all investigated molecules were determined by reverse transcriptase-real-time polymerase chain reaction.

Results

All three micro RNAs exhibited highest expression levels in benign SGTs, whereas miR-26a And miR-191 were significantly more expressed in PAs compared to WTs (p = 0.045 and p = 0.029, respectively). PLAG1 And HIF2 were both overexpressed in WTs compared to PAs (p = 0.048 and p = 0.053, respectively). Bioinformatic analysis suggested that all investigated micro RNAs function as negative regulators of MTDH.

Conclusion

The results of this study suggest that all three micro RNAs have a considerable negative impact on MTDH oncogene expression in malignant tumors, while the differences between levels of miR-26a, miR-191, PLAG1, and HIF2 in PA and WT represent possible differential diagnosis markers.

背景：唾液腺肿瘤（SGTs）是一类异质性病变，在鉴别诊断和治疗方面仍是一项挑战。尽管组织学检查结果决定着 SGTs 的治疗，但分子改变的检测正成为一种有效的补充工具。本研究旨在分析三种微RNA（miR-26a、miR-26b和miR-191）和三种促癌分子标记物（PLAG1、MTDH和HIF2）在SGTs和正常唾液腺（NSG）组织中的相对表达水平，并评估它们作为潜在鉴别诊断标记物的作用：这项横断面研究包括 58 名 SGT 患者（23 名多形性腺瘤患者、27 名 Warthin 肿瘤患者和 8 名恶性 SGT 患者）和 10 名对照组（正常唾液腺组织）。通过逆转录酶实时聚合酶链反应测定了所有研究分子的相对基因表达水平：结果：所有三种微小 RNA 在良性 SGTs 中的表达水平最高，而 miR-26a 和 miR-191 在 PAs 中的表达明显高于 WTs（分别为 p = 0.045 和 p = 0.029）。与 PAs 相比，PLAG1 和 HIF2 在 WTs 中均表达过高（分别为 p = 0.048 和 p = 0.053）。生物信息学分析表明，所有研究的微RNA都是MTDH的负调控因子：本研究结果表明，所有三种微小 RNA 对恶性肿瘤中 MTDH 致癌基因的表达都有相当大的负面影响，而 PA 和 WT 中 miR-26a、miR-191、PLAG1 和 HIF2 水平的差异是可能的鉴别诊断标志物。

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引用次数: 0

The effects of enoxaparin treatment in a xenograft mouse model of oral squamous cell carcinoma: A pilot study 依诺肝素治疗对口腔鳞状细胞癌异种移植小鼠模型的影响：一项试验研究。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-06-09 DOI: 10.1111/jop.13563

Yeliz Ekici, Merva Soluk-Tekkesin, Umut Can Küçüksezer, Hazal Banu Olgun Celebioglu, Erman Bulent Tuncer, Elcin Bedeloglu, Feyza Nur Tuncer

Background

Recent studies suggest that enoxaparin may have therapeutic effects on oral squamous cell carcinoma. We aimed to assess this effect utilizing xenograft mouse model through evaluations of proliferation and angiogenesis markers at the RNA and protein levels.

Methods

Mice were divided into enoxaparin treatment (n = 4), positive control (n = 4) and negative control (n = 3) groups. Immunohistochemical analyses were performed utilizing Bcl-2, Bax and Ki-67 antibodies. Expression levels of proliferation and apoptosis related genes were calculated utilizing qRT-PCR. Time-dependent proliferation assays were performed in OSC-19 and HEK293 cell-lines.

Results

Bax antibody showed positive staining in the cytoplasm and nuclei of tumor cells, while Bcl-2 antibody displayed staining only in the cytoplasm. A proliferation index of 15%–20% was found in all groups with the Ki-67 marker indicating no metastasis. Enoxaparin treatment caused decrease in BCL2, BAX and CCNB1 genes' expressions. Compared to HEK293, proliferation assays demonstrated higher division rates in OSC-19 with a significant decrease in viability after 96 h.

Conclusion

Reduced BCL-2 expression indicates a regression of tumor growth, but reduced BAX expression is not correlated with increased apoptosis. Despite the aggressive nature of OSC-19, our results showed a low cell viability with a high division rate when compared with the control HEK293. This paralleled our in vivo findings that showed absence of lymph node metastasis across all mice groups. This discrepancy with the literature suggests that further investigations of the underlying mechanisms and protein-level analyses are needed to draw definitive conclusions about the effect of enoxaparin on OSC-19 behavior.

背景：最近的研究表明，依诺肝素可能对口腔鳞状细胞癌有治疗作用。我们旨在利用异种移植小鼠模型，通过在 RNA 和蛋白质水平上评估增殖和血管生成标记物来评估这种作用：小鼠分为依诺肝素治疗组（n = 4）、阳性对照组（n = 4）和阴性对照组（n = 3）。使用 Bcl-2、Bax 和 Ki-67 抗体进行免疫组化分析。利用 qRT-PCR 计算增殖和凋亡相关基因的表达水平。在 OSC-19 和 HEK293 细胞系中进行了时间依赖性增殖试验：结果：Bax 抗体在肿瘤细胞的细胞质和细胞核中均呈阳性染色，而 Bcl-2 抗体仅在细胞质中染色。各组的增殖指数均为 15%-20%，Ki-67 标记显示无转移。依诺肝素治疗会导致 BCL2、BAX 和 CCNB1 基因表达量减少。与 HEK293 相比，增殖试验表明 OSC-19 的分裂率更高，96 小时后存活率显著下降：结论：BCL-2 表达的减少表明肿瘤生长的减弱，但 BAX 表达的减少与细胞凋亡的增加并不相关。尽管 OSC-19 具有侵袭性，但与对照组 HEK293 相比，我们的结果显示细胞存活率低，分裂率高。这与我们的体内研究结果一致，即所有小鼠组都没有淋巴结转移。这种与文献报道的差异表明，要就依诺肝素对 OSC-19 行为的影响得出明确结论，还需要进一步研究其潜在机制并进行蛋白质水平分析。

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引用次数: 0

Feasibility study of ResNet-50 in the distinction of intraoral neural tumors using histopathological images ResNet-50 利用组织病理学图像区分口腔内神经肿瘤的可行性研究。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-06-04 DOI: 10.1111/jop.13560

Giovanna Calabrese dos Santos, Anna Luíza Damaceno Araújo, Henrique Alves de Amorim, Daniela Giraldo-Roldán, Sebastião Silvério de Sousa-Neto, Pablo Agustin Vargas, Luiz Paulo Kowalski, Alan Roger Santos-Silva, Marcio Ajudarte Lopes, Matheus Cardoso Moraes

Background

Neural tumors are difficult to distinguish based solely on cellularity and often require immunohistochemical staining to aid in identifying the cell lineage. This article investigates the potential of a Convolutional Neural Network for the histopathological classification of the three most prevalent benign neural tumor types: neurofibroma, perineurioma, and schwannoma.

Methods

A model was developed, trained, and evaluated for classification using the ResNet-50 architecture, with a database of 30 whole-slide images stained in hematoxylin and eosin (106, 782 patches were generated from and divided among the training, validation, and testing subsets, with strategies to avoid data leakage).

Results

The model achieved an accuracy of 70% (64% normalized), and showed satisfactory results for differentiating two of the three classes, reaching approximately 97% and 77% as true positives for neurofibroma and schwannoma classes, respectively, and only 7% for perineurioma class. The AUROC curves for neurofibroma and schwannoma classes was 0.83%, and 0.74% for perineurioma. However, the specificity rate for the perineurioma class was greater (83%) than in the other two classes (neurofibroma with 61%, and schwannoma with 60%).

Conclusion

This investigation demonstrated significant potential for proficient performance with a limitation regarding the perineurioma class (the limited feature variability observed contributed to a lower performance).

背景：神经肿瘤很难仅凭细胞性质进行区分，通常需要免疫组化染色来帮助确定细胞系。本文研究了卷积神经网络对神经纤维瘤、会厌瘤和裂隙瘤这三种最常见的良性神经肿瘤类型进行组织病理学分类的潜力：方法：使用 ResNet-50 架构开发、训练和评估了一个分类模型，数据库包含 30 张经苏木精和伊红染色的全切片图像（106,782 个补丁由训练子集、验证子集和测试子集生成和划分，并采取了避免数据泄漏的策略）：该模型的准确率为 70%（归一化为 64%），在区分三个类别中的两个类别方面取得了令人满意的结果，神经纤维瘤和裂隙瘤类别的真阳性率分别达到约 97% 和 77%，而会厌瘤类别的真阳性率仅为 7%。神经纤维瘤和分裂瘤的 AUROC 曲线为 0.83%，会厌瘤为 0.74%。然而，会厌瘤类别的特异性率（83%）高于其他两个类别（神经纤维瘤为 61%，分裂瘤为 60%）：这项研究表明，会厌瘤类别的准确性具有很大的潜力，但也存在局限性（观察到的特征变异性有限，导致准确性较低）。

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引用次数: 0

Oral cancer detection and progression prediction using noninvasive cytology-based DNA ploidy approach 利用基于无创细胞学的 DNA 倍性方法检测和预测口腔癌的进展。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-06-02 DOI: 10.1111/jop.13562

Kelly Y. P. Liu, Samson Ng, Maryam Taleghani, Sarah Y. Zhu, Anita Carraro, Zhaoyang Chen, Branko Palcic, Catherine F. Poh, Martial Guillaud

Background

Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions.

Methods

This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers. Brushing cells were processed to characterize DNA ploidy. A two-step DNA ploidy-based algorithm, the DNA ploidy oral cytology (DOC) test, was developed using a training set, and verified in test and validation sets to differentiate high-grade lesions (HGLs) from normal. The prognostic value of the test was evaluated by an independent outcome cohort, including progressed and non-progressing normal, reactive and low-grade lesions. Classification performance was assessed by accuracy, sensitivity, and specificity, while the prognostic value was evaluated by using the Cox proportional hazards analysis on 3-year progression-free survival (PFS).

Results

The developed DOC test exhibited high accuracy for detecting HGLs in the test and validation sets, with a sensitivity of 0.97 and 0.96, respectively. Its application to the Outcome cohort demonstrated significant prognostic value for 3-year PFS (log rank, p < 0.001). Multivariate analysis showed that high-grade pathology was the only variable explaining positive DOC test, not age, smoking, or lesional site.

Conclusion

Clinical implementation of the DOC test could provide an effective screening method for detecting HGLs for biopsy and lesions at risk of progression.

背景：尽管口腔很容易触及，但口腔癌（OC）仍然是一个沉重的负担。本研究的目的是开发一种基于 DNA 倍体的细胞学检测方法，用于早期检测高风险口腔病变：这项回顾性研究使用了从 95 例正常和 474 例临床异常粘膜（活检诊断为反应性、低级别或高级别癌前病变或癌症）采集的 569 份口腔刷牙样本。对刷牙细胞进行了处理，以确定 DNA 倍性的特征。利用训练集开发了一种基于DNA倍性的两步算法--DNA倍性口腔细胞学（DOC）测试，并在测试集和验证集中进行了验证，以区分高级别病变（HGL）和正常病变。该测试的预后价值由一个独立的结果队列进行评估，包括进展和非进展的正常、反应性和低级别病变。通过准确性、灵敏度和特异性评估了分类效果，而通过对3年无进展生存期（PFS）的Cox比例危险分析评估了预后价值：结果：所开发的 DOC 检验在测试集和验证集中检测 HGL 的准确性很高，灵敏度分别为 0.97 和 0.96。将其应用于 "结果 "队列，对3年PFS具有显著的预后价值（对数秩，p 结论：DOC测试在临床上的应用对HGL具有显著的预后价值：DOC测试的临床应用可为活组织检查和有进展风险的病变提供一种有效的筛查方法。

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引用次数: 0

Artificial intelligence and radiomics in the diagnosis of intraosseous lesions of the gnathic bones: A systematic review 人工智能和放射组学在诊断胫骨骨内病变中的应用：系统综述。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-05-28 DOI: 10.1111/jop.13548

Daniela Giraldo-Roldán, Anna Luíza Damaceno Araújo, Matheus Cardoso Moraes, Viviane Mariano da Silva, Erin Crespo Cordeiro Ribeiro, Matheus Cerqueira, Cristina Saldivia-Siracusa, Sebastião Silvério Sousa-Neto, Maria Eduarda Pérez-de-Oliveira, Marcio Ajudarte Lopes, Luiz Paulo Kowalski, André Carlos Ponce de Leon Ferreira de Carvalho, Alan Roger Santos-Silva, Pablo Agustin Vargas

Background

The purpose of this systematic review (SR) is to gather evidence on the use of machine learning (ML) models in the diagnosis of intraosseous lesions in gnathic bones and to analyze the reliability, impact, and usefulness of such models. This SR was performed in accordance with the PRISMA 2022 guidelines and was registered in the PROSPERO database (CRD42022379298).

Methods

The acronym PICOS was used to structure the inquiry-focused review question “Is Artificial Intelligence reliable for the diagnosis of intraosseous lesions in gnathic bones?” The literature search was conducted in various electronic databases, including PubMed, Embase, Scopus, Cochrane Library, Web of Science, Lilacs, IEEE Xplore, and Gray Literature (Google Scholar and ProQuest). Risk of bias assessment was performed using PROBAST, and the results were synthesized by considering the task and sampling strategy of the dataset.

Results

Twenty-six studies were included (21 146 radiographic images). Ameloblastomas, odontogenic keratocysts, dentigerous cysts, and periapical cysts were the most frequently investigated lesions. According to TRIPOD, most studies were classified as type 2 (randomly divided). The F1 score was presented in only 13 studies, which provided the metrics for 20 trials, with a mean of 0.71 (±0.25).

Conclusion

There is no conclusive evidence to support the usefulness of ML-based models in the detection, segmentation, and classification of intraosseous lesions in gnathic bones for routine clinical application. The lack of detail about data sampling, the lack of a comprehensive set of metrics for training and validation, and the absence of external testing limit experiments and hinder proper evaluation of model performance.

背景：本系统性综述（SR）旨在收集机器学习（ML）模型用于诊断胫骨骨内病变的证据，并分析此类模型的可靠性、影响和实用性。本研究按照 PRISMA 2022 指南进行，并在 PROSPERO 数据库（CRD42022379298）中注册：方法：使用首字母缩写词 PICOS 来构建以探究为重点的综述问题 "人工智能在诊断咬肌骨内病变方面是否可靠？文献检索在各种电子数据库中进行，包括 PubMed、Embase、Scopus、Cochrane Library、Web of Science、Lilacs、IEEE Xplore 和 Gray Literature（Google Scholar 和 ProQuest）。使用 PROBAST 对偏倚风险进行了评估，并通过考虑数据集的任务和抽样策略对结果进行了综合：结果：共纳入 26 项研究（21 146 幅放射影像）。釉母细胞瘤、牙源性角化囊肿、牙源性囊肿和根尖周囊肿是最常见的病变。根据 TRIPOD，大多数研究被归类为第 2 类（随机划分）。只有 13 项研究提供了 F1 评分，这些研究提供了 20 项试验的指标，平均值为 0.71 (±0.25)：结论：没有确凿证据支持基于 ML 的模型在常规临床应用中用于检测、分割和分类咬肌骨内病变。数据取样缺乏细节、缺乏一套全面的训练和验证指标，以及缺乏外部测试都限制了实验的进行，阻碍了对模型性能的正确评估。

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引用次数: 0

Radiation-induced exosomes promote oral squamous cell carcinoma progression via enhancing SLC1A5-glutamine metabolism 辐射诱导的外泌体通过增强SLC1A5-谷氨酰胺代谢促进口腔鳞状细胞癌的进展

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-05-27 DOI: 10.1111/jop.13561

Rongchun Yang, Siyuan Zhang, Lixuan Wang, Yingyao Chen, Xiaobing Chen, Juan Xia, Xianyue Ren, Bin Cheng, Xijuan Chen

Background

Radiotherapy (RT) can drive cancer cells to enter a state of cellular senescence in which cells can secrete senescence-associated secretory phenotype (SASP) and produce small extracellular vesicles (sEVs) to interact with cells in the tumor microenvironment (TME). Tumor-derived sEVs that are taken up by recipient cells contribute to cancer cell metabolic plasticity, resistance to anticancer therapy, and adaptation to the TME. However, how radiation-induced sEVs support oral squamous cell carcinoma (OSCC) progression remains unclear.

Methods

Beta-galactosidase staining and SASP mRNA expression analysis were used to evaluate the senescence-associated activity of OSCC cells after irradiation. Nanoparticle tracking analysis was performed to identify radiation-induced sEVs. Liquid chromatography–tandem mass spectrometry (LC–MS) was used to explore changes in the levels of proteins in radiation-induced sEVs. Cell Counting Kit-8 and colony formation assays were performed to investigate the function of radiation-induced SASP and sEVs in vitro. A xenograft tumor model was established to investigate the functions of radiation-induced sEVs and V-9302 in vivo as well as the underlying mechanisms. Bioinformatics analysis was performed to determine the relationship between glutamine metabolism and OSCC recurrence.

Results

We determined that the radiation-induced SASP triggered OSCC cell proliferation. Additionally, radiation-induced sEVs exacerbated OSCC cell malignancy. LC–MS/MS and bioinformatics analyses revealed that SLC1A5, which is a cellular receptor that participates in glutamine uptake, was significantly enriched in radiation-induced sEVs. In vitro and in vivo, inhibiting SLC1A5 could block the oncogenic effects of radiation-induced sEVs in OSCC.

Conclusion

Radiation-induced sEVs might promote the proliferation of unirradiated cancer cells by enhancing glutamine metabolism; this might be a novel molecular mechanism underlying radiation resistance in OSCC patients.

背景：放疗（RT）可促使癌细胞进入细胞衰老状态，在这种状态下，细胞可分泌衰老相关分泌表型（SASP）并产生小细胞外囊泡（sEVs），与肿瘤微环境（TME）中的细胞相互作用。被受体细胞吸收的肿瘤衍生小泡有助于癌细胞的代谢可塑性、抗癌治疗的耐受性以及对肿瘤微环境的适应性。然而，辐射诱导的sEV如何支持口腔鳞状细胞癌（OSCC）的进展仍不清楚：方法：采用β-半乳糖苷酶染色和SASP mRNA表达分析评估OSCC细胞在辐照后的衰老相关活性。纳米粒子追踪分析用于识别辐射诱导的sEVs。液相色谱-串联质谱法（LC-MS）用于研究辐射诱导的sEVs中蛋白质水平的变化。为了研究辐射诱导的 SASP 和 sEVs 在体外的功能，进行了细胞计数试剂盒-8 和集落形成试验。建立了异种移植肿瘤模型，以研究辐射诱导的 sEVs 和 V-9302 在体内的功能及其内在机制。通过生物信息学分析确定谷氨酰胺代谢与 OSCC 复发之间的关系：结果：我们发现辐射诱导的 SASP 会引发 OSCC 细胞增殖。此外，辐射诱导的 sEVs 加剧了 OSCC 细胞的恶性程度。LC-MS/MS和生物信息学分析表明，参与谷氨酰胺摄取的细胞受体SLC1A5在辐射诱导的sEVs中显著富集。在体外和体内，抑制 SLC1A5 可阻断辐射诱导的 sEVs 对 OSCC 的致癌作用：结论：辐射诱导的sEVs可能会通过增强谷氨酰胺代谢来促进未受辐射癌细胞的增殖；这可能是OSCC患者耐辐射的一种新的分子机制。

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引用次数: 0

circMTO1/miR-30c-5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast–myofibroblast transition circMTO1/miR-30c-5p/SOCS3 轴通过抑制成纤维细胞-肌成纤维细胞转化减轻口腔黏膜下纤维化。

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-05-27 DOI: 10.1111/jop.13559

Xin Bin, Jing-Yi Cheng, Zhi-Yuan Deng, Bo Li, Xing-Huan-Yu Xu, Ou-Sheng Liu, Zhangui Tang

Background

circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF.

Methods

Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH).

Results

circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast–myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002.

Conclusion

circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.

背景：circRNA已被证明参与多种疾病的治疗；然而，它们在口腔黏膜下纤维化（OSF）这一潜在恶性疾病中的作用仍不明显。我们的初步实验检测了湖南省湘雅口腔医院采集的OSF组织（20例）和正常粘膜组织（20例）中circRNA线粒体翻译优化1同源物（circMTO1）的表达，结果显示OSF组织中circMTO1的表达显著下降。因此，我们进一步探讨了circMTO1在OSF中的表达：方法：采用RT-qPCR和Western印迹法检测靶分子的表达。采用伤口愈合和 Transwell 试验评估颊粘膜成纤维细胞（BMFs）的迁移和侵袭。使用双荧光素酶、RNA 免疫沉淀（RIP）和 RNA 拉取试验评估了 miR-30c-5p、circMTO1 和 SOCS3 之间的相互作用。结果发现：在 OSF 患者和arecoline 刺激的 BMFs 中，circMTO1 和 SOCS3 的表达量减少，而 miR-30c-5p 的表达量增加。circMTO1的过表达能有效抑制成纤维细胞-肌成纤维细胞转化（FMT），表现为Coll I、α-SMA和Vimentin的表达增加，以及BMFs的迁移和侵袭功能减弱。机理研究表明，circMTO1 通过疏导 miR-30c-5p 增强 SOCS3 的表达，进而使 FAK/PI3K/AKT 通路失活，从而抑制 FMT。结论：circMTO1/miR-30c-5p/SOCS3轴通过FAK/PI3K/AKT通路调节异丙啉处理的BMFs中的FMT。扩大样本量和体内验证可进一步阐明它们作为 OSF 治疗靶点的潜力。

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引用次数: 0

Erythroblast transformation-specific-related gene promotes metastasis of oral squamous cell carcinoma by transcriptionally upregulating peroxiredoxin 1 红细胞转化特异性相关基因通过转录上调过氧化物酶1促进口腔鳞状细胞癌转移

IF 2.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2024-05-26 DOI: 10.1111/jop.13544

Yujia Gu, Xue Chen, Mei Tian, Ke Liu

Background

Some studies confirmed that erythroblast transformation-specific-related gene (ERG) may be a pathogenic factor of oral squamous cell carcinoma (OSCC). However, the undergoing molecular mechanism has not been elucidated yet.

Objective

In this study, the investigation will focus on how the transcription factor ERG modulates the biological behaviors of OSCC.

Methods

In this study, cancer tissue specimens and corresponding paracancer tissues were collected from 54 patients. Real-time polymerase chain reaction analysis and Western blots were employed to detect the expression of multiple genes. Cell proliferation assays, Transwell, and flow cytometry assay were utilized to detect the proliferation, invasion, and apoptosis of OSCC cell, respectively. Dual luciferase reporter gene and chromatin immunoprecipitation assays were conducted to verify the regulation of ERG on PRDX1.

Results

ERG exhibits high expression levels in OSCC. Inhibition of ERG has been shown to effectively suppress the malignant growth of OSCC cells. Moreover, ERG has been found to transcriptionally upregulate the expression of PRDX1. The knockdown of PRDX1 has demonstrated its ability to inhibit the malignant growth of OSCC cells. Interestingly, when PRDX1 is overexpressed, it attenuates the inhibitory effect of si-ERG on the malignant growth of OSCC cells. This suggests that PRDX1 may play a crucial role in mediating the impact of ERG on malignancy in OSCC cells.

Conclusion

The transcription factor ERG promotes the expression of PRDX1, which could enhance the proliferation and invasion while inhibiting the apoptosis of OSCC cells.

背景：一些研究证实，红细胞转化特异性相关基因（ERG）可能是口腔鳞状细胞癌（OSCC）的致病因素之一。然而，其分子机制尚未阐明：本研究将重点探讨转录因子 ERG 如何调节 OSCC 的生物学行为：方法：本研究收集了 54 例患者的癌组织标本和相应的癌旁组织。采用实时聚合酶链反应分析和 Western 印迹检测多个基因的表达。利用细胞增殖试验、Transwell 和流式细胞术分别检测 OSCC 细胞的增殖、侵袭和凋亡。通过双荧光素酶报告基因和染色质免疫沉淀实验来验证ERG对PRDX1的调控作用：结果：ERG在OSCC中呈现高表达水平。结果：ERG在OSCC中呈高表达水平，抑制ERG可有效抑制OSCC细胞的恶性生长。此外，研究还发现ERG能转录上调PRDX1的表达。PRDX1的敲除证明了其抑制OSCC细胞恶性生长的能力。有趣的是，当PRDX1过表达时，它会减弱si-ERG对OSCC细胞恶性生长的抑制作用。这表明，PRDX1可能在介导ERG对OSCC细胞恶性生长的影响中发挥了关键作用：结论：转录因子ERG可促进PRDX1的表达，从而在抑制OSCC细胞凋亡的同时增强其增殖和侵袭能力。

{"title":"Erythroblast transformation-specific-related gene promotes metastasis of oral squamous cell carcinoma by transcriptionally upregulating peroxiredoxin 1","authors":"Yujia Gu, Xue Chen, Mei Tian, Ke Liu","doi":"10.1111/jop.13544","DOIUrl":"10.1111/jop.13544","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Some studies confirmed that erythroblast transformation-specific-related gene (<i>ERG</i>) may be a pathogenic factor of oral squamous cell carcinoma (OSCC). However, the undergoing molecular mechanism has not been elucidated yet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this study, the investigation will focus on how the transcription factor <i>ERG</i> modulates the biological behaviors of OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, cancer tissue specimens and corresponding paracancer tissues were collected from 54 patients. Real-time polymerase chain reaction analysis and Western blots were employed to detect the expression of multiple genes. Cell proliferation assays, Transwell, and flow cytometry assay were utilized to detect the proliferation, invasion, and apoptosis of OSCC cell, respectively. Dual luciferase reporter gene and chromatin immunoprecipitation assays were conducted to verify the regulation of ERG on <i>PRDX1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>ERG</i> exhibits high expression levels in OSCC. Inhibition of ERG has been shown to effectively suppress the malignant growth of OSCC cells. Moreover, ERG has been found to transcriptionally upregulate the expression of <i>PRDX1</i>. The knockdown of <i>PRDX1</i> has demonstrated its ability to inhibit the malignant growth of OSCC cells. Interestingly, when <i>PRDX1</i> is overexpressed, it attenuates the inhibitory effect of si-<i>ERG</i> on the malignant growth of OSCC cells. This suggests that <i>PRDX1</i> may play a crucial role in mediating the impact of <i>ERG</i> on malignancy in OSCC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The transcription factor ERG promotes the expression of <i>PRDX1</i>, which could enhance the proliferation and invasion while inhibiting the apoptosis of OSCC cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0